PHOSPHODIEASERASE INHIBITION DECREASES NEURONAL

磷酸酶抑制可减少神经元

• 批准号: 12671422
• 负责人: OGATA Tadanori
• 金额: $ 1.28万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671422/
• 关键词: spinal cord; nitric oxide; neuron; cyclic GMP; phosphodiesterase; phosphodiesterase; cyclic AMP; TNF-α; アストロサイト; マイクログリア

The effect of intracellular cyclic GMP increase on neuronal damage was tested using a newly developed nitric oxide-related injury model of cultured spinal cord neurons. Neuronal damage after 24 hours' exposure to sodium nitroprusside (SNP, 6.25-100 μM), an NO donor, was evaluated by measuring the activity of released lactate dehydrogenase (LDH) from degenerated neurons. The intracellular cyclic GMP increase caused by the addition of 100 μM 8-bromo-cyclic GMP, a cell membrane permeable cyclic GMP, strongly inhibited the neuronal damage induced by 10 μM SNP, although 8-bromo-cyclic AMP yielded no effect. The addition of 8-bromo-cyclic GMP induced nerve growth factor (NGF) production in cultured neurons, suggesting that the neuroprotection via intracellular cyclic GMP increase is mediated by NGF production. The addition of propentofylline (PPF; 1-100 μM), a xanthine derivative and phosphodiesterase (PDE) inhibitor, enhanced intracellular cyclic GMP elevation induced by SNP exposure. The neuronal damage induced by 10 μM SNP exposure for 24 hours was almost completely blocked in the presence of PPF.

细胞内环状GMP增加对神经元损伤的影响通过新开发的一氧化氮相关的培养脊髓神经元模型进行了测试。通过测量来自退化神经元的释放的裂解脱氢酶（LDH）的活性，评估了24小时暴露于硝普钠（SNP，6.25-100μM）后的神经元损伤（6.25-100μM）。添加100 µM 8-溴-Cycle GMP（一种细胞膜可渗透的循环GMP）强烈抑制了10μMSNP诱导的神经元损伤，尽管8-Bromo-Cycle AMP无产生效果，但细胞膜周期GMP的添加是可渗透的细胞膜GMP（一种细胞膜渗透的环境GMP）引起的。在培养的神经元中添加了8-溴-Cycle GMP诱导的神经生长因子（NGF）产生，这表明NGF的产生介导了通过细胞内循环GMP增加的神经保护作用。添加倾向基（PPF；1-100μM），一种黄氨酸衍生物和磷酸二酯酶（PDE）抑制剂，增强了由SNP暴露引起的细胞内环状GMP升高。在PPF存在下，几乎完全阻止了10μMSNP暴露诱导的神经元损伤。